On October 3, 2023 Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence (AI) company developing targeted and transformative cancer therapies using its proprietary AI and machine learning (ML) platform, RADR, with multiple clinical stage drug programs, reported that in vivo data highlighting the enhanced efficacy of Lantern’s drug candidate LP-184 in glioblastoma (GBM) were published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Lantern Pharma, OCT 3, 2023, View Source [SID1234635604]). LP-184 is a unique small molecule with low nanomolar activity and favorable CNS penetration. LP-184 utilizes its powerful mechanism of action, known as synthetic lethality, to exploit common vulnerabilities in solid tumor and CNS cancers with DNA damage repair (DDR) deficiencies. In addition, Lantern’s AI platform, RADR, has highlighted overlapping gene dependency profiles between GBM tumorigenesis and sensitivity to LP-184, such as EGFR activation pathways.

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"The data highlighted in Clinical Cancer Research solidify LP-184 as a promising therapeutic for GBM, with LP-184 having inhibited the viability and growth of multiple GBM models including temozolomide-resistant and MGMT-expressing cells," stated Panna Sharma, Lantern’s President and CEO. "The rapid advancement of LP-184 into a first-in-human Phase 1 trial provides strong validation of the power of our AI-enabled approach to drug development. This approach is about more than just developing new treatments, it’s about making them more targeted, more effective, and ultimately doing all of this more efficiently. This publication demonstrates our ability to deliver on these aspirations and introduce new therapeutic programs in areas where there is significant unmet patient need."

The article, entitled "Preclinical Efficacy of LP-184, a Tumor Site Activated Synthetic Lethal Therapeutic, in Glioblastoma" can be accessed here.

A Phase 1 clinical trial (NCT05933265) evaluating LP-184 in patients with advanced solid tumors is underway. The single arm multicenter trial is assessing the safety and tolerability of escalating doses of LP-184 to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) in patients with advanced solid tumors and recurrent high-grade gliomas, including GBM. The study has been designed as a 35 patient trial with patients receiving LP-184 infusion on Day 1 and Day 8 of each 21-day cycle, for a minimum of two cycles. Patients will be monitored for safety, pharmacokinetics, and clinical activity, and dose escalation is planned with a minimum of three patients per cohort. Lantern anticipates the Phase 1A portion of the trial to be completed in the first half of 2024 and a Phase 2 trial in GBM and other CNS cancers to begin in the second half of 2024. The anticipated Phase 2 trial will be conducted by Starlight Therapeutics, a wholly owned subsidiary of Lantern focused entirely on CNS and brain cancer indications. Lantern estimates that LP-184 has a global aggregate market potential of approximately $11-13 billion, consisting of $6-7 billion for solid tumors and $5-6 billion for CNS cancers.

About LP-184:

LP-184 is a unique small molecule that utilizes its powerful mechanism of action, known as synthetic lethality, to exploit common vulnerabilities in solid tumor and CNS cancers with DNA damage repair (DDR) deficiencies. The anti-tumor potential of LP-184 has been demonstrated across an extensive number of in-vitro and in-vivo cancer models, including pancreatic, prostate, lung, triple-negative breast cancer (TNBC), glioblastoma (GBM), brain metastases, and ATRT. In addition to LP-184’s promise as a single agent, its antitumor potency has the potential to be enhanced when used in combination with existing FDA-approved agents and other treatment modalities including spironolactone, PARP inhibitors, and radiation therapy. Results validating LP-184’s anti-tumor potential have been published at leading conferences and journals including, the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, Clinical Cancer Research, an AACR (Free AACR Whitepaper) journal, the Society for Neuro-Oncology annual meeting, the San Antonio Breast Cancer Symposium, and the Frontiers in Drug Discovery Journal.

On October 3, 2023 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, reported that it has reached agreement with the U.S. Food and Drug Administration (FDA) on plans for submission of a New Drug Application (NDA) for UGN-102 (mitomycin) for intravesical solution (Press release, UroGen Pharma, OCT 3, 2023, View Source [SID1234635603]). The FDA indicated that the current clinical development plan for UGN-102, which includes evaluation of duration of complete response (CR) at 12 months from the pivotal ENVISION trial, will support submission of an NDA for the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The FDA also agreed that the UGN-102 NDA can utilize a rolling review, allowing for early submission of the Chemistry, Manufacturing and Controls (CMC) sections of the NDA, which is planned for January 2024. If approved, UGN-102 has the potential to introduce a new non-surgical treatment paradigm for LG-IR-NMIBC, a subset of bladder cancer patients characterized by high recurrence rates and the need for multiple surgeries.

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"We are very pleased with the outcome of our pre-NDA meeting where the FDA agreed with our plan to submit our NDA for UGN-102 once all patients reach 12 months post CR. Our dialogue with the FDA during our recent pre-NDA meeting was very constructive and underscores the strength of our clinical program for UGN-102," said Liz Barrett, President and CEO, UroGen. "With the announcement of positive Phase 3 topline results from the ATLAS and ENVISION studies earlier this year, this meeting was a significant step in defining the path forward for NDA submission and potential approval for UGN-102. UroGen is committed to developing innovative treatments for those battling bladder cancer, one of the most recurrent malignancies, and UGN-102 stands at the forefront of that mission."

The UGN-102 clinical development plan centers around the Phase 3 ENVISION pivotal trial and is supported by robust clinical data from the ATLAS Phase 3 and OPTIMA Phase 2b trials.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting. Assuming positive findings from the durability of response endpoint from the ENVISION Phase 3 study, UroGen anticipates submitting an NDA for UGN-102 in 2024.

On October 3, 2023 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage biotechnology company advancing novel, oral, non-systemically absorbed biotherapeutics to transform the care of serious diseases, reported the closing of its previously announced underwritten public offering (Press release, Synlogic, OCT 3, 2023, View Source [SID1234635602]).

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The offering consisted of 7,394,363 shares of common stock (or pre-funded warrants to purchase common stock in lieu thereof) and accompanying common warrants to purchase up to 7,394,363 shares of common stock. The combined effective offering price to the public of each share of common stock (or pre-funded warrant) and accompanying warrant was $2.84. The accompanying warrants have an exercise price of $3.408 per share, will be exercisable immediately, and will expire five years from the initial exercise date. The aggregate gross proceeds to Synlogic from the public offering were approximately $21.0 million, prior to deducting underwriting discounts, commissions and other estimated offering expenses. Participants in the offering included new and existing investors. Chardan acted as sole book-running manager for the offering.

Synlogic anticipates existing cash and cash equivalents and the proceeds from this offering will be sufficient to fund planned operations into the first half of 2025.

The Securities and Exchange Commission ("SEC") declared effective a registration statement on Form S-1 relating to these securities on September 27, 2023. A final prospectus relating to this offering was filed with the SEC. The offering was made only by means of a prospectus. Copies of the prospectus relating to the offering may be obtained from Chardan Capital Markets, LLC, 17 State Street, Suite 2130, New York, New York 10004, at (646) 465-9000, or by email at [email protected]. Investors may also obtain these documents at no cost by visiting the SEC’s website at View Source

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On October 3, 2023 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that harness the power of the tumor microenvironment to overcome tumor immune evasion and drug resistance, reported clinical updates from its dose escalation portion of the Phase 1/2 study of NT219, a first in class dual inhibitor of Insulin receptor substrate (IRS) 1/2 and Signal Transducer and Activator of Transcription 3 (STAT3) and provides its outlook for planning the next clinical development steps with NT219 for second-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head & Neck (R/M SCCHN) (Press release, Purple Biotech, OCT 3, 2023, View Source [SID1234635601]).

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The Phase 1/2 study (NCT04474470), an open-label, dose escalation and expansion study is designed to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of NT219 as a monotherapy and in combination with Erbitux (cetuximab), in patients with R/M SCCHN, or with advanced colorectal cancer. Forty-nine patients were enrolled in five dose levels (3, 6, 12, 24 and 50 mg/kg); 27 in the monotherapy arm, and 22 in the combination therapy with cetuximab. Patients in both cohorts were dosed to the highest NT219 dose level of 50mg/kg. No dose-limiting toxicities (DLTs) were reported in either cohort and NT219 was well tolerated as a monotherapy and in combination with cetuximab.

A dose-dependent increase in drug exposure of NT219 was reported. The exposure achieved at the highest dose level of 50mg/kg was within the efficacy range of the human equivalent dose level as predicted from preclinical models. Inhibition of intra-tumoral IRS 1/2 and STAT3, NT219’s targets, was demonstrated in patients’ biopsies.

Among the four R/M SCCHN patients dosed at 50mg/kg of NT219 in combination with cetuximab, that were evaluable for efficacy, two patients demonstrated confirmed partial response by response evaluation criteria in solid tumors (RECIST) 1.1. Other results from the Phase 1/2 study will be provided at one of the upcoming medical conferences.

"We believe these results are very encouraging given the low response rate to cetuximab as monotherapy in recurrent/metastatic SCCHN patients in the second/third line," said Ari Rozenberg, M.D, University of Chicago and study Investigator. "While still early, we are excited to see responders at the highest NT219 dose level where we expected the appropriate exposure to be attained, along with evidence of on target treatment effect in patients’ biopsies. I look forward to continuing investigating NT219 and seeing more data in this disease setting with urgent need for improved therapies."

Treatment options for patients who had progressed following treatment with immunotherapy in first line R/M SCCHN are limited, with mostly cetuximab and chemotherapy currently available. The Company is in the process of designing a Phase 2 study of NT219 in combination with cetuximab in 2L R/M SCCHN. Such a study may evaluate NT219 in combination with cetuximab with or without standard of care chemotherapy following progression after immunotherapy in first line treatment.

Gil Efron, Purple Biotech CEO, added, "I am very satisfied with the observed activity of NT219 in recurrent and/or metastatic SCCHN patients. Due to the dire unmet need in this difficult to treat population, we believe that extending these early results through a robust proof of concept study would be meaningful for patients and for Purple Biotech and may lead us to next development steps. We will continue exploring higher dose optimization while designing our next study. We believe that the good tolerability of NT219 in combination with cetuximab can position this combination as a strong candidate to combine with other agents in 2L SCCHN and to achieve better survival for patients. Additionally, as demonstrated by our preclinical data, we believe that this data could potentially pave the way for development of NT219 in combination with EGFR inhibitors or other agents such as a-PD1 and KRAS inhibitors, potentially unlocking the full potential of NT219."

On October 3, 2023 Biodexa Pharmaceuticals PLC, (Nasdaq: BDRX), a clinical stage biopharmaceutical company developing a pipeline of products aimed at primary and metastatic cancers of the brain, reported that it has completed recruitment into cohort A of its ongoing Phase 1 study of MTX110 (also known as MAGIC-G1 study)(NCT 05324501) in patients with recurrent glioblastoma (rGBM) (Press release, Biodexa Pharmaceuticals, OCT 3, 2023, View Source [SID1234635600]).

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MAGIC-G1 is an open-label, dose escalation study designed to assess the feasibility and safety of intermittent infusions of MTX110 administered by convection enhanced delivery (CED) via implanted refillable pump and catheter. The study aims to recruit two cohorts (A and B), with a minimum of four patients in each; while patients in both cohorts receive MTX110 via intermittent repeated CED infusions, patients in the B cohort will be allowed CED catheter repositioning upon first in-study clinical and/or radiographic confirmed progression.

Following review by the Data Safety Monitoring Board (DSMB), the dose was escalated to 90µM after the first patient in cochort A and, because there have been no dose-limiting toxicities, recruitment into this cohort has concluded with the minimum of four patients. Patient 1 received 13 treatment cycles over 19 weeks of study treatment period, whereas patient 2 received 10 cycles over 13 weeks of study treatment period; patient 3 has, to date, received five cycles of treatment. The fourth patient underwent surgery yesterday and will receive their first cyle of treatment imminently.

Enrolment in cohort B will commence upon approval by the study DSMB, which is anticipated to be received towards the end of October 2023.

In addition, the Company is planning to add two more investigational centres into the study with activation expected in December 2023 and January 2024, respectively.

Commenting, Dr Dmitry Zamoryakhin, MD, MBA, CSO of Biodexa, said: "We are delighted to have concluded the recruitment of cohort A with the minimum number of patients based on the absence of drug-related adverse events. Cohort B of the study will provide a unique opportunity of continuous CED treatment after in-study tumour progression, which will be the first of its kind."

About Glioblastoma ("GB")

GB is the most common and devastating primary malignant brain tumour in adults encompassing 14.3% of all primary brain and central nervous system neoplasms(1). With an incidence of approximately 3.2 per 100,000 population in the USA, approximately 12,300 people in the USA will be diagnosed with GB per annum. Standard of care for treatment of GB is typically maximal surgical resection followed by radiotherapy plus concomitant and maintenance temozolomide chemotherapy with or without the Optune device. Notwithstanding, the multidisciplinary approach, almost all patients experience tumour progression with nearly universal mortality. The median survival from initial diagnosis is less than 21 months(2).

Currently, no standard of care is established for rGB.

Sources:
(1) Low JT, Ostrom QT, Cioffi G, Neff C, Waite KA, Kruchko C, Barnholtz-Sloan JS. Primary brain and other central nervous system tumors in the United States (2014-2018): A summary of the CBTRUS statistical report for clinicians. Neurooncol Pract. 2022 Feb 22;9(3):165-182. doi: 10.1093/nop/npac015. PMID: 35601966; PMCID: PMC9113389.
(2) Stupp R, Taillibert S, Kanner AA, et al. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA : the journal of the American Medical Association. 2015;314(23):2535-2543.
Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709-722.

About MTX110

MTX110 is a water-soluble form of panobinostat free base, achieved through complexation with hydroxypropyl-β-cyclodextrin (HPBCD), that enables convection-enhanced delivery (CED) at potentially chemotherapeutic doses directly to the site of the tumour. Panobinostat is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). The currently available oral formulation of panobinostat lactate (Farydak) is not suitable for treatment of brain cancers owing to poor blood-brain barrier penetration and inadequate brain drug concentrations. Based on favourable translational science data, MTX110 is being evaluated clinically as a treatment for recurrent glioblastoma (NCT05324501), paediatric DMG (NCT04264143) and recurrent medulloblastoma (NCT04315064). MTX110 is delivered directly into and around the patient’s tumour via a catheter system (e.g. CED or fourth ventricle infusions) to bypass the blood-brain barrier. This technique exposes the tumour to very high drug concentrations while simultaneously minimising systemic drug levels and the potential for toxicity and other side effects. Panobinostat has demonstrated high potency against DIPG and GBM tumour cells in in vitro and in vivo models, and in a key study it was the most promising of 83 anticancer agents tested in 14 patient-derived DIPG cell lines (Grasso et al, 2015. Nature Medicine 21(6), 555-559).